Gynecomastia with spironolactone

Doses should be titrated at intervals no more frequent than every 2 to 3 days. Because spironolactone is used for its antialdosterone effects, much higher doses (up to 400 mg/day) are used than those used when treating hypertension. If intolerable side effects such as gynecomastia occur with spironolactone, other potassium-sparing diuretics may be used, but clinical trials have not shown equivalent efficacy.22... 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

Synthetic steroids may cause endocrine abnormalities by actions on other steroid receptors. Gynecomastia, impotence, and benign prostatic hyperplasia all have been reported with spironolactone. Such effects have not been reported with eplerenone because it is much more selective than spironolactone for the mineralocorticoid receptor, being virtually inactive on androgen or progesterone receptors. 

Epierenone has been reported to produce less gynecomastia than spironolactone (6,7). In patients with gynecomastia from spironolactone, epierenone can be substituted and gynecomastia status reassessed. 

Mann, N. (1963) Gynecomastia during therapy with spironolactone. Journal of the American Medical Association, 184, 778-780. 

Gynecomastia may be associated with the use of spironolactone and is reversible upon withdrawal of the dmg. 

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease tiie elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in tiie male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain. 

Potassium-sparing diuretics may cause hyperkalemia, especially in patients with chronic kidney disease or diabetes, and in patients receiving concurrent treatment with an ACE inhibitor, ARB, NSAID, or potassium supplement. Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria. Spironolactone may cause gynecomastia in up to 10% of patients, but this effect occurs rarely with eplerenone. 

The diuretic effect of spironolactone develops fully only with continuous administration for several days. Two possible explanations are (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone (2) an inhibition of aldosterone-stimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia (enlargement of male breast). Clinical uses include conditions of increased aldosterone secretion, e.g., liver cirrhosis with ascites. 

Adverse effects Renal function may deteriorate with the decreased circulating fluid volume, especially after the addition of another diuretic drug acting on the RAAS system, and careful monitoring of serum creatinine is essential. Serum potassium should be monitored within one week of initiation and at least every four weeks for the first three months and every three months thereafter. It should also be monitored at any dose change in spironolactone or if there is a change in concomitant medications that affects the potassium balance. The spironolactone dose (standard 25 mg per day) should be reduced if potassium levels are <5.4 mEq/L, and treatment should be discontinued if painful gynecomastia or serious renal dysfunction or hyperkalemia result. 

The only frequent adverse effects were gynecomastia, breast pain, or both in 10% of men. The rate of discontinuation because of these events was 2%. The risk of gynecomastia should not be an argument against the use of spironolactone in men with severe heart failure, since it reduces both morbidity and death. 

The results from EPHESUS have raised the question of which aldosterone blocker, spironolactone or eplerenone, should be used preferentially. Currently, there are no data to support that the more selective but more expensive eplerenone is superior to or should be preferred to the less expensive generic spironolactone unless a patient has experienced gynecomastia, breast pain, or impotence while receiving spironolactone. Einally, it should be noted that hyperkalemia is just as likely to appear with both these agents. 

Antiandrogenic and progestational symptoms such as gynecomastia, impotence and menstrual irregularities related to the clinical use of spironolactone were observed already at a very early stage [7], and recognized since 1975 as characteristic adverse effects due to the unspecific interactions of spironolactone with the AR and PR [8]. 

Spironolactone (e.g., Aldactone) Antagonist of aldosterone (aldosterone causes Na+ retention). Also has actions similar to amiloride. Used with thiazides for edema (in congestive heart failure), cirrhosis, and nephrotic syndrome. Also to treat or diagnose hyperaldosteronism. As for amiloride. Also causes endocrine imbalances (acne, oily skin, hirsutism, gynecomastia)... 

The primary concern with the use of spironolactone is the development of hyperkalemia, which can be fatal. Spironolactone may cause hypersensitivity reactions, gastrointestinal disturbances, peptic ulcer, gynecomastia, decreased libido, and impotence. It also has been implicated in tumor production during chronic toxicity studies in rats, but human risk has not been documented. 

Breasts In 175 patients with resistant hypertension who took spironolactone 25-100 mg/ day adverse reactions that were attributed to spironolactone included gynecomastia or breast discomfort in seven as a result spironolactone was withdrawn in six (3.4%) one man had reduced libido [25 ]. 

Of 168 patients with mild-to-moderate heart failure (NYHA class I-II) and left ventricular ejection fraction 40% or less who were randomized to spironolactone mean dose 52 mg/day or placebo, spironolactone was withdrawn in two patients with gynecomastia and breast tenderness [26 "]. 

The effect of spironolactone, in combination with other medications, on recurrent atrial fibrillation has been evaluated in 164 consecutive patients, mean age 66 years, in a randomized 12-month trial there was gynecomastia in three patients who took spironolactone the plasma potassium concentration did not change significantly [32 ]. 

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